Methotrexate for Cutaneous Sarcoidosis: A Dermatology-Based Case Series of 23 Patients

Dear Editor

Sarcoidosis is a debilitating multisystem granulomatous disease of unknown etiology. ¹ While cutaneous disease occurs in up to one-third of sarcoidosis patients and can be disfiguring, treatment outcome data are sparse. ² In a 2020 study, three of four cutaneous sarcoidosis patients treated with methotrexate (MTX) achieved minimal clinically important differences. ² Other MTX for cutaneous sarcoidosis studies (performed in 1995 [n = 17] and 1977 [n = 16]) reported encouraging response rates of 94% and 100%, respectively. ^3,4 We assessed the response to MTX of 23 patients with cutaneous sarcoidosis.

Wake Forest Baptist Health Institutional Review Board approval was obtained to perform a retrospective medical record review of patients who received MTX for cutaneous sarcoidosis between 2010 and 2020. Patients without biopsy-proven sarcoidosis and without follow-up were excluded. Outcomes were categorized as: complete clearance (absence of active lesions, possibly with post-inflammatory hyperpigmentation), partial response (fewer lesions, less erythema, reduction in size of nodules or flattening of papules/plaques), no response.

The patients were primarily white (65%) and female (70%), with a mean age of 53 ± 11 years (Supplemental Table 1). Several patients had concomitant systemic disease (13 pulmonary, 6 ocular, 1 hepatic, 1 cardiac, 1 laryngeal, 1 parotid gland). Cutaneous manifestations most commonly presented on the upper extremities (14/23; 61%), face (12/23; 52%), and lower extremities (11/23; 48%); morphologies included plaque (7/23; 30%), papular (7/23; 30%), nodular (4/23; 17%), subcutaneous (3/23; 13%), and maculopapular (3/23; 13%) lesions. Four patients presented with lupus pernio (4/23; 17%), and none had erythema nodosum. Skin disease began a median of 2.2 years before initiation of MTX, which was dosed at a median of 12.5 mg weekly for a median of 22 months. Many patients were treated with other agents prior to MTX (13 prednisone, 9 hydroxychloroquine, 1 dapsone, 1 colchicine, 1 azathioprine).

Twenty-one patients improved (91%) within a median 2 months, and 17 (74%) completely cleared within a median 8 months. These timeframes are comparable to previous reports. ⁵ Three of four patients with lupus pernio improved, including 1 who completely cleared. Many responders were on MTX monotherapy (13/21; 62%). Five responders received concomitant systemic therapies (2 adalimumab, 2 hydroxychloroquine, 1 thalidomide, 1 prednisone [5 milligrams once daily]), and 3 received concomitant topical therapies (1 clobetasol, 1 desonide, and 1 triamcinolone plus tacrolimus). Nine (9/21; 43%) responders flared (median follow-up evaluation 21 months [range 0-126] from time of initial improvement to most recent visit); 8 flared during MTX therapy (4/8 were associated with dose reduction trials), and 1 flared upon MTX discontinuation.

MTX was generally well-tolerated; gastrointestinal upset, nausea, and fatigue each occurred 3 times. Transiently elevated liver enzymes were detected in two patients, with a maximum aspartate aminotransferase (AST) of 68 U/L and a maximum alanine aminotransferase (ALT) of 72 U/L. One patient’s white blood cell count dropped to 3.1 (x 10⁹ per liter) while on MTX.

Although this study is limited by a small sample size and its retrospective design, MTX appears to be an effective steroid-sparing treatment for cutaneous sarcoidosis.

Supplemental Material

Online supplementary file 1 - Supplemental material for Methotrexate for Cutaneous Sarcoidosis: A Dermatology-Based Case Series of 23 Patients

Supplemental material, Online supplementary file 1, for Methotrexate for Cutaneous Sarcoidosis: A Dermatology-Based Case Series of 23 Patients by Matthew L. Hrin, Josiah A. Williams, Nathan L. Bowers, Joseph L. Jorizzo, Steven R. Feldman and William W. Huang in Journal of Cutaneous Medicine and Surgery